FDA Approves 1st Generic Version Of EpiPen

Silver Spring, Maryland, USA :The U.S. Food and Drug Administration (FDA) today approved the first generic version of EpiPen and EpiPen Jr (epinephrine) auto-injector for the emergency treatment of allergic reactions, including those that are life-threatening (anaphylaxis), in adults and pediatric patients who weigh more than 33 pounds. Teva Pharmaceuticals USA gained approval to market its generic epinephrine auto-injector in 0.3 mg and 0.15 mg strengths.

“Today’s approval of the first generic version of the most-widely prescribed epinephrine auto-injector in the U.S. is part of our longstanding commitment to advance access to lower cost, safe and effective generic alternatives once patents and other exclusivities no longer prevent approval,” said FDA Commissioner Scott Gottlieb, M.D.

“This approval means patients living with severe allergies who require constant access to life-saving epinephrine should have a lower-cost option, as well as another approved product to help protect against potential drug shortages. The path to developing generic drug-device combination products like this one is challenging. We remain committed to doing our part to provide scientific and regulatory clarity for sponsors seeking to develop complex generics, as well as prioritize the approval of medicines with little or no generic competition as part of our overarching effort to remove barriers to generic development and market entry of critically important medicines. Many of these steps were outlined in our Drug Competition Action Plan, announced last year. We’re especially committed to the development of generic copies of complex products. These products can be hard to copy, and therefore sometimes don’t face timely generic competition once patents and exclusivities are no longer a block to approval. We’re advancing new guidance for sponsors to make the development of generic versions of complex products more efficient, and we’re prioritizing review of many complex generic drug applications.” Gottlieb added.

Life-threatening allergies can include reactions to insect bites or stings, foods, medications, latex or other causes. Anaphylaxis is a medical emergency that affects the whole body and, in some cases, leads to death. Anaphylaxis occurs in approximately one in 50 Americans. People who have had an anaphylaxis episode always face the risk of another one. Because of this risk, they must carry an emergency dose of epinephrine at all times. Many must keep more than one dose at hand.

The EpiPen is intended to automatically inject a dose of epinephrine into a person’s thigh to stop an allergic reaction. The FDA has approved several epinephrine auto-injector products under new drug applications to treat anaphylaxis, including EpiPen, Adrenaclick and Auvi-Q. In addition, “authorized generic” versions of EpiPen and Adrenaclick are marketed without the brand names. An authorized generic is made under the brand name’s existing new drug application using the same formulation, process and manufacturing facilities that are used by the brand name manufacturer. The labeling or packaging is, however, changed to remove the brand name or other trade dress. In some cases, a company may choose to sell an authorized generic at a lower cost than the brand-name drug product.

Epinephrine auto-injector products are known as “combination products” because they consist of a drug (epinephrine) and a device (the auto-injector). The development of generic combination products can be more challenging than typical drug products, and the FDA regularly takes steps to help guide industry through the process. The agency works with individual companies to support their development of such complex products, and creates publicly available guidance describing the steps the FDA recommends companies take to submit complete, approvable applications for various types of medical products. In this case, the FDA has published three draft or final guidances since 2009 related to the development of generic epinephrine auto-injectors. In addition, as with brand-name drugs, the FDA inspects manufacturing and packaging facilities for generic drugs to ensure that they are capable of consistently producing quality products.

This epinephrine injection (auto-injector) is intended for immediate administration to patients. When given intramuscularly or subcutaneously, it has a rapid onset and short duration of action. Epinephrine works by reducing swelling in the airway and increasing blood flow in the veins.

The most common side effects associated with epinephrine injection are anxiety, apprehensiveness, restlessness, tremor, weakness, dizziness, sweating, palpitations, pallor, nausea and vomiting, headache and/or respiratory difficulties. Rare cases of serious skin and soft tissue infections have been reported following use of the drug. In patients with heart disease, use of epinephrine injection may cause chest pain (angina pectoris) or abnormal heart beats (ventricular arrhythmias). Following use of epinephrine injection, patients should seek immediate medical or hospital care. Epinephrine should not be injected into the vein, buttock, fingers, hands or feet. To minimize risk of injection-site injury, movement of the leg should be limited during injection.

The agency requires appropriate data and information to demonstrate that complex drug-device combination products meet the FDA’s rigorous approval standards to ensure quality drug products that are safe and effective are available to patients.

The FDA, an agency within the U.S. Department of Health and Human Services, protects the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products for human use, and medical devices. The agency also is responsible for the safety and security of our nation’s food supply, cosmetics, dietary supplements, products that give off electronic radiation, and for regulating tobacco products.

Jennifer Madsen, head of federal advocacy for the Food Allergy Research & Education advocacy group based in Virginia, said about 15 millions Americans, including six million children, have food allergies. Of those, Ms. Madsen estimated that potentially 2.4 million children have had a life-threatening incident. Her organization has been pushing the F.D.A. to approve a generic EpiPen for a long time.

“We’re very excited to have this big win for the food allergy community,” she said. “Particularly in view of this national shortage.”

In May, after scores of consumers reported that they couldn’t buy EpiPens, the F.D.A. announced there were shortages of two types of epinephrine auto-injectors, including Mylan’s EpiPen, and Adrenaclick, made by Impax Laboratories. The agency attributed the shortages to manufacturing problems.

Another brand, called Auvi-Q, was available, but was not covered by as many insurance policies.

The EpiPen has had a troubled history.

And Mylan itself, stung by congressional inquiries and criticism, released its own generic version that costs about half as much. In August of last year, Mylan announced that it had finalized a $465 million settlement with the Justice Department about claims that it overcharged the federal government for the product.

Last September, the F.D.A. accused the drugmaker Pfizer, which manufactures the EpiPen for Mylan, of failing to properly investigate reports of EpiPen malfunctions, including cases in which patients became severely ill or died after the device did not work. An F.D.A. warning to Pfizer said that Meridian Medical Technologies, which is a unit of the drug giant, did not adequately examine problems with a critical component of the EpiPen, the mechanism that insures that it fires and delivers the proper dose.

At the time, a Pfizer spokeswoman said the company was confident in the EpiPen’s safety and efficacy, and said it had no information to indicate that there was any causal connection between the product complaints and any patient deaths.